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PP2A and DUSP6 are involved in sphingosylphosphorylcholine-induced hypopigmentation

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Abstract

Activation of extracellular signal-related kinase (ERK) is involved in decreased melanogenesis by sphingosylphosphorylcholine (SPC). In the present study, we confirmed that SPC activated ERK and that a specific inhibitor of the ERK pathway (PD98059) recovered SPC-induced hypopigmentation. Moreover, we found that SPC significantly reduces protein phosphatase 2A (PP2A) activity in Mel-Ab cells, and that PP2A activator treatment abrogated SPC-induced hypopigmentation. We determined that α-melanocyte-stimulating hormone (α-MSH) increased the expression of dual-specificity phosphatase 6 (DUSP6), an ERK phosphatase, in a time-dependent manner. In contrast, SPC decreased the level of DUSP6 in Mel-Ab cells. Furthermore, inhibiting DUSP6 increased ERK activation and subsequently augmented the SPC-induced hypopigmenting effects. Taken together, our data suggest that SPC-induced phosphatase inhibition is also responsible for the hypopigmentary effects.

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Abbreviations

α-MSH:

α-Melanocyte-stimulating hormone

BSA:

Bovine serum albumin

CT:

Cholera toxin

DUSP6:

Dual-specificity phosphatase 6

ERK:

Extracellular signal-regulated kinase

FBS:

Fetal bovine serum

MAPKs:

Mitogen-activated protein kinases

MITF:

Microphthalmia-associated transcription factor

PP2A:

Protein phosphatase 2A

SPC:

Sphingosylphosphorylcholine

TPA:

12-O-Tetradecanoylphorbol-13-acetate

TRP:

Tyrosinase-related protein

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Acknowledgments

This study was supported by a grant (A100179) from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea.

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Authors and Affiliations

  1. Department of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseok-dong Dongjak-gu, Seoul, 156-756, Republic of Korea

    Hyo-Soon Jeong & Dong-Seok Kim

  2. Department of Dermatology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Kyoungki-do, 463-707, Republic of Korea

    Kyoung-Chan Park

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Correspondence to Dong-Seok Kim.

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Jeong, HS., Park, KC. & Kim, DS. PP2A and DUSP6 are involved in sphingosylphosphorylcholine-induced hypopigmentation. Mol Cell Biochem 367, 43–49 (2012). https://doi.org/10.1007/s11010-012-1317-8

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  • DOI: https://doi.org/10.1007/s11010-012-1317-8

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